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In the five chapters of this dissertation, I investigate the paleobiology of SouthAmerican native ungulates (SANUs) and caviomorph rodents. Although these studies involve different taxonomic groups and employ disparate methods, most rely on previously undescribed fossils to interrogate broader evolutionary questions. In the first chapter, I describe early Miocene litopterns (a group of SANUs) from Pampa Castillo, Aysén Region, Chile, and perform a phylogenetic analysis of one of its subgroups, Proterotheriidae. Litoptern taxa from Pampa Castillo include the macraucheniid Theosodon and proterotheriids Thoatherium and Picturotherium, corroborating the fauna’s assignment to the Santacrucian South American land mammal age (SALMA). My phylogenetic analysis, which indicates that “Anisolambdidae” forms a non-monophyletic cluster within Proterotheriidae, is the foundation of a new stem-based definition for Proterotheriidae. This chapter was published in the Journal of Systematic Palaeontology in 2020. My second chapter describes two new proterotheriids from the middle Miocene of Quebrada Honda, Tarija Department, Bolivia, and analyzes litoptern diversity and body size evolution in a phylogenetic context. These taxa, Olisanophus riorosarioensis gen. et sp. nov. and Olisanophus akilachuta gen. et sp. nov., greatly clarify proterotheriid evolution in mid-latitude South America. The diversity analysis indicates that these groups were more diverse than previously appreciated, particularly during the Paleogene. Macraucheniids increased in body size throughout the Cenozoic, whereas proterotheriids followed a similar trend during the Paleogene, but did not change in size during the Neogene. This chapter was published in Ameghiniana in 2020. Cavioid, chinchilloid, and erethizontoid caviomorph rodents from Pampa Castillo are described in the third chapter. Cavioids are represented by Luantus minor, Eocardia cf. excavata, and Neoreomys australis, the last of which is the most abundantly represented mammal in the Pampa Castillo fauna. Chinchilloids are represented by four species of Perimys (P. erutus, P. onustus, P. intermedius, and a yet unnamed species previously described from the Pinturas Formation), Prolagostomus pusillus, Scleromys quadrangulatus, and a probable new species of Scleromys. This assemblage represents a mixture of two well-known, contemporaneous fossil faunas previously recognized from the lower + middle sequences of the Pinturas Formation and the Santa Cruz Formation. The phylogenetic affinities and relative abundance of these taxa suggest the paleoenvironment of Pampa Castillo was similarly intermediate between these two better-known faunas. In the fourth chapter, I describe the octodontoid caviomorphs from Pampa Castillo and conduct a faunal similarity analysis of Pampa Castillo and ten other early to middle Miocene (Colhuehuapian–Friasian/Colloncuran SALMAs) Patagonian rodent faunas. Eight octodontoids occur at Pampa Castillo, three of them likely representing new species of Caviocricetus, Dudumus, and Prostichomys. The other five are referred to previously described taxa: Acarechimys minutus, Acarechimys constans, Acarechimys cf. minutissimus, Acaremys cf. murinus, and Spaniomys cf. riparius. Faunal similarity analyses yielded inconsistent results depending on whether genus- or species-level data were used. The combined results of these analyses and recently published geochronological data suggest that the ‘Pinturan’ biochronologic interval is not valid; faunas referred to it should instead be assigned to the Santacrucian SALMA. I analyze the proximal ankle bones of litoptern and notoungulate (another SANU group) from the early Miocene Santa Cruz Formation, Argentina with the aim of assessing their utility in systematic studies and whether linear measurements or twodimensional (2D) landmarks are more effective for assessing morphological differences. The ultimate goal of this research is to allow robust inferences about the locomotory habits of the sampled taxa. These results suggest that isolated tarsals may be identified to family and genus-level, but this conclusion needs further testing. Quantitative tests show that tarsals of different SANU taxa may be slightly more reliably distinguished by 2D landmarks than by linear measurements. However, 2D landmarks are clearly superior from the perspective of ease of measurement, replicability, and applicability to taxonomically diverse samples. Although the lack of modern taxa in the sample limited the paleobiological inferences that could be drawn, body mass, phylogeny, and possibly locomotor behavior, clearly influence tarsal morphology. Throughout this dissertation, I have used the description of new taxa and specimens as the foundation for phylogenetic, paleoenvironmental, biochronological, and ecomorphological analyses. These studies have advanced our knowledge of mammal evolution in South America, particularly in the early and middle Miocene.